Abstract
Hepatitis B virus (HBV) infection is an important factor causing hepatocellular carcinoma (HCC). The aim of this study was to investigate the metabolic characteristics and related metabolic enzyme changes during the progression from chronic hepatitis B (CHB) to liver cirrhosis (LC) and, ultimately, to HCC. An untargeted metabolomics assay was performed in plasma from 50 healthy volunteers, 43 CHB patients, 67 LC patients, and 39 HCC patients. A total of 24 differential metabolites (DMs) were identified. Joint pathway analysis suggested striking changes in amino acid metabolism and lipid metabolism from CHB to HCC. The panel of L-serine, creatine and glycine distinguished LC from CHB, and L-serine, cystathionine, creatine and linoleic acid distinguished HCC from LC. Bioinformatic analysis of publicly available data showed that differential metabolite profile-associated enzyme genes, including alanine-glyoxylate aminotransferase-2 (AGXT2), D-amino-acid oxidase (DAO), and cystathionine gamma-lyase (CTH), were downregulated, while bisphosphoglycerate mutase (BPGM), cystathionine-β-synthase (CBS), phosphoserine phosphatase (PSPH) and acyl-CoA thioesterase 7 (ACOT7) were upregulated, in HCC, all of which correlated with a poor prognosis for HCC patients. Our results indicated that serum metabolites and related enzymes are of considerable significance for the diagnosis and prognosis of HCC and can provide a theoretical basis and therapeutic index for future diagnosis and treatment.
Highlights
It is estimated that one out of three people worldwide have been infected with hepatitis B virus (HBV), and approximately 240 million to 350 million of them will progress to chronic hepatitis [1]
Two hundred six patients were separated into 4 groups, including the healthy group (n = 50), chronic hepatitis B (CHB) group (n = 43), HBV-associated Liver cirrhosis (LC) group (n = 67) and HBV-associated hepatocellular carcinoma (HCC) group (n = 39)
The results showed that the four groups were well differentiated, except for some samples from the CHB group and LC group, and the four groups were arranged from left to right according to the development from healthy to HCC, indicating that the metabolic profiles in patients change gradually with the development of HBV infection-associated diseases
Summary
It is estimated that one out of three people worldwide have been infected with hepatitis B virus (HBV), and approximately 240 million to 350 million of them will progress to chronic hepatitis [1]. People have been able to effectively prevent HBV infection since the introduction of the hepatitis B vaccine in 1982 [2], approximately 1 million people that die from hepatitis B-related chronic liver disease each year [3]. Most patients with chronic hepatitis have no obvious symptoms but have the opportunity to develop cirrhosis or even hepatocellular carcinoma (HCC) [4]. Liver cirrhosis (LC) is a long-term pathological process, and one of the main causes of LC is chronic hepatitis B (CHB).
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